Childhood encephalitis in the Greater Mekong region: critical to public health policy
Authors: Kyaw Zin Thant, Mya Myat Ngwe Tun
Journal: The Lancet Global Health (2022)

Acute encephalitis syndrome is a serious public health issue because of its high mortality and frequent occurrence of long-term neurological side-effects. It occurs at a higher incidence in children than in adults.1Granerod J Crowcroft NS The epidemiology of acute encephalitis.Neuropsychol Rehabil. 2007; 17: 406-428Crossref PubMed Scopus (94) Google Scholar Southeast Asia is a biodiverse region, with an increasing human population and growing urbanisation. Furthermore, the region is at high risk for pathogen emergence because of frequent contact with wildlife and domesticated animals.2Lam WK Zhong NS Tan WC Overview on SARS in Asia and the world.Respirology. 2003; 8: S2-S5Crossref PubMed Scopus (84) Google Scholar Surveillance, diagnosis, and control of encephalitis remain inadequate in most low-income and middle-income countries in southeast Asia. In The Lancet Global Health, Jean David Pommier and colleagues3Pommier JD Gorman C Crabol Y et al.Childhood encephalitis in the Greater Mekong region (the SouthEast Asia Encephalitis Project): a multicentre prospective study.Lancet Glob Health. 2022; 10: e989-1002Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar report the findings of a 3-year multicentre prospective study of childhood encephalitis using comprehensive and harmonised microbiological diagnostic techniques across four public health referral laboratories, one in each of Cambodia, Laos, Vietnam, and Myanmar. To our knowledge, this is the largest study to date to identify the cause of encephalitis among children aged 28 days to 16 years. Of 664 children included (343 [52%] in Cambodia, 203 [31%] in Vietnam, 62 [9%] in Laos, and 56 [8%] in Myanmar), a confirmed or probable cause of encephalitis was identified in 425 (64%) children: 216 (33%) of 664 cases were due to Japanese encephalitis virus, 27 (4%) were due to dengue virus, 26 (4%) were due to influenza virus, 24 (4%) were due to herpes simplex virus 1, 18 (3%) were due to Mycobacterium tuberculosis, 17 (3%) were due to Streptococcus pneumoniae, 17 (3%) were due to enterovirus A71 (EV-A71), 74 (9%) were due to other pathogens, and six (1%) were due to autoimmune encephalitis. A larger proportion of cases in Cambodia than in Vietnam were due to Japanese encephalitis virus (164 [48%] of 343 vs 33 [16%] of 203), 119 (18%) of 664 cases were treatable, and 276 (42%) could have been prevented by vaccination. The expanded program on immunization (EPI) provides the following vaccines in six countries in the Greater Mekong region (Cambodia, Vietnam, Myanmar, Laos, Thailand, and Yunnan province in China): tuberculosis; diphtheria, tetanus, and pertussis; hepatitis B; Haemophilus influenzae type b (except for China); polio; measles, mumps, and rubella; and Japanese encephalitis virus. Vaccination policy varies among the countries. Pommier and colleagues found high rates of vaccine-preventable infections (due to Japanese encephalitis virus, influenza virus, and tuberculosis) that should encourage study countries to strengthen national vaccination programmes. Given that rapid and early diagnosis for treatable acute encephalitis is crucial, Pommier and colleagues diagnosed causes for 83 (13%) of 664 children within 24 h of study inclusion, screening for 68 pathogens by PCR or serology using cerebrospinal fluid (CSF), blood, and nasopharyngeal, throat, and rectal swabs. Further studies are needed that investigate more cases per day, since this study only included one child per day per site; the inclusion of more than one child per site per day could potentially identify higher detection rates than was found here. Pommier and colleagues also addressed the study population's exposure to animals. Children with Japanese encephalitis often had pigs and chickens in their compounds and were less likely to have been vaccinated against the virus. 432 (74%) of 581 patients who were discharged from hospital were followed-up at 1 year, of whom 24 (6%) had died, 129 (30%) had developed neurological sequelae, and 279 (65%) had recovered. Among studies of confirmed or probable causes of encephalitis focusing on adults or children in Thailand, the leading pathogens were: Japanese encephalitis virus, enteroviruses, and Orientia tsutsugamushi in CSF samples for the period 2003–05; enteroviruses, Epstein-Barr virus, varicella zoster virus, cytomegalovirus, herpes simplex virus, and dengue virus from CSF samples of patients for the period 2002–18; and N-methyl-D-aspartate receptor-associated encephalitis for the period 2007–17.4Olsen SJ Supawat K Campbell AP et al.Japanese encephalitis virus remains an important cause of encephalitis in Thailand.Int J Infect Dis. 2010; 14: e888-e892Summary Full Text Full Text PDF PubMed Scopus (48) Google Scholar, 5Hemachudha P Petcharat S Hinjoy S Saraya AW Hemachudha T Encephalitis in Thailand: a neglected disease increasingly caused by enterovirus.Trop Med Infect Dis. 2021; 6: 117Crossref PubMed Scopus (2) Google Scholar, 6Pruetarat N Netbaramee W Pattharathitikul S Veeravigrom M Clinical manifestations, treatment outcomes, and prognostic factors of pediatric anti-NMDAR encephalitis in tertiary care hospitals: a multicenter retrospective/prospective cohort study.Brain Dev. 2019; 41: 436-442Summary Full Text Full Text PDF PubMed Scopus (15) Google Scholar Most cases of acute meningitis in adults from Thailand were caused by cryptococcosis, followed by tuberculosis in 2013–17.7Aimbudlop K Bruminhent J Kiertiburanakul S Infectious causes of acute meningitis among Thai adults in a university hospital.J Infect Chemother. 2021; 27: 198-204Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar Few studies of childhood acute encephalitis have been done in Yunnan province. EPI established a Japanese encephalitis virus vaccination programme in 2008 and the overall incidence of infection with Japanese encephalitis virus in Yunnan decreased between 2007 and 2017; however, children younger than 10 years still had a high rate of Japanese encephalitis virus infection.8Mao X Zhou H The spatiotemporal distribution of Japanese encephalitis cases in Yunnan Province, China, from 2007 to 2017.PLoS One. 2020; 15e0231661Crossref Scopus (3) Google Scholar EPI has not been well distributed in regions with limited supplies of vaccines. Adult vaccination against Japanese encephalitis virus in Yunnan is unrealistic and unsustainable.8Mao X Zhou H The spatiotemporal distribution of Japanese encephalitis cases in Yunnan Province, China, from 2007 to 2017.PLoS One. 2020; 15e0231661Crossref Scopus (3) Google Scholar EV-A71 vaccines were introduced in Yunnan in 2016. The vaccination rate increased among children younger than 5 years; non-EV-A71 and non-coxsackievirus A16 enteroviruses appeared to be the predominant strains, and the incidence of infections with these strains increased in Yunnan from 2008 to 2019.9Jiang L Jiang H Tian X Xia X Huang T Epidemiological characteristics of hand, foot, and mouth disease in Yunnan Province, China, 2008–2019.BMC Infect Dis. 2021; 21: 751Crossref PubMed Scopus (5) Google Scholar Most cases of acute bacterial meningitis occur during childhood. The most prevalent pathogens in Yunnan from 2012 to 2015 were Escherichia coli, S pneumoniae, Staphylococcus epidermidis, H influenzae type b, and group B streptococcus.10Jiang H Su M Kui L et al.Prevalence and antibiotic resistance profiles of cerebrospinal fluid pathogens in children with acute bacterial meningitis in Yunnan province, China, 2012–2015.PLoS One. 2017; 12e0180161Google Scholar However, further work is needed to understand childhood encephalitis in Yunnan province. Overall, financial support, comprehensive diagnostic procedures, pathogens treatable with specific therapies, and enhanced vaccination coverage present the major challenges to tackling the childhood encephalitis burden. Improving clinical acumen (eg, lumbar puncture to obtain CSF samples) and upgrading laboratory facilities (eg, laboratory automation, superior imaging facilities, and next-generation sequencing) are important for sustainability. Antimicrobial resistance is also an important consideration when choosing treatment approaches, such as when treating patients with M tuberculosis. In the long term, rehabilitation of affected patients is important, not only for themselves and their family, but also for society and the community. Therefore, public health policy makers must be advised on how to manage antimicrobial resistance. We declare no competing interests. KZT and MMNT contributed equally to the writing of this Comment. Childhood encephalitis in the Greater Mekong region (the SouthEast Asia Encephalitis Project): a multicentre prospective studyIn southeast Asia, most causes of childhood encephalitis are either preventable or treatable, with Japanese encephalitis virus being the most common cause. We provide crucial information that could guide public health policy to improve diagnostic, vaccination, and early therapeutic guidelines on childhood encephalitis in the Greater Mekong region. Full-Text PDF Open Access